Brain IGFBP-5 modifies the relation of depressive symptoms to decline in cognition in older persons
Brain IGFBP-5 modifies the relation of depressive symptoms to decline in cognition in older persons
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DOI：
10.1016/j.jad.2019.03.051
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发表时间：
2019-05-01
影响因子：
6.6
通讯作者：
Arvanitakis, Zoe
中科院分区：
文献类型：
--
作者：
Capuano, Ana W.;Wilson, Robert S.;Arvanitakis, Zoe
背景：脑蛋白质，包括胰岛素样生长因子结合蛋白5(IGFBP-5)，与衰老中的认知功能障碍有关。将抑郁与认知联系起来的机制还知之甚少。我们假设抑郁症状与认知之间的联系是由脑蛋白质介导或修饰的。方法：对1057名已故受试者进行IGFBP-5、HSPB2、AK4、ITPK1和PLXNB1的测定，这些受试者每年平均接受抑郁症状和认知评估8.9年。每个人在被诊断为痴呆症之前，每年的平均抑郁症状数被计算出来。结果：IGFBP5的平均值高出1个标准差，出现更多抑郁症状的几率增加14%(p<；0.031)。更高的IGFBP5与控制抑郁症状的整体认知(p<；0.001)和五个认知领域(p<；0.008)的下降速度有关。胰岛素样生长因子结合蛋白-5缓解了抑郁症状与整体认知能力下降的关系(p=0.045)。在抑郁症状对整体认知和认知领域下降的总影响中，IGFBP5的中介作用不超过10%(p>；0.070)。限制：参与者是志愿者，自我选择的偏见限制了我们研究结果的普适性。此外，我们使用了关于抑郁症状的自我报告数据。然而，我们也使用了关于抑郁药物的数据作为敏感性分析来证实这一发现。结论：在老年，大脑IGFBP-5与抑郁症状和认知有关。抑郁症状与认知能力下降的关联取决于IGFBP-5。
Background: Brain proteins, including Insulin-like Growth Factor Binding Protein 5 (IGFBP-5), have been associated with cognitive dysfunction in aging. Mechanisms linking depression with cognition are poorly understood. We hypothesize that the association of depressive symptoms with cognition is mediated or modified by brain proteins.Methods: IGFBP-5, HSPB2, AK4, ITPK1 and PLXNB1 were measured in dorsolateral prefrontal cortex in 1057 deceased participants, who underwent annual assessments of depressive symptoms and cognition for a mean of 8.9 years. The average number of depressive symptoms per year before a dementia diagnosis was calculated for each person.Results: A one standard deviation above the mean IGFBP-5 was associated with a 14% higher odds of having more depressive symptoms (p < 0.031). Higher IGFBP-5 was associated with faster decline in global cognition (p < 0.001) and five cognitive domains (p < 0.008), controlling for depressive symptoms. IGFBP-5 moderated the association of depressive symptoms with decline in global cognition (p= 0.045). IGFBP-5 mediated ten percent or less of the total effect of depressive symptoms on decline in global cognition and the cognitive domains (p > 0.070).Limitations: Participants were volunteers and self-selection bias limits the generalizability of our findings. In addition, we used self-reported data on depressive symptoms. However, we also used data on depression medications as sensitivity analyses to confirm findings.Conclusions: In old age, brain IGFBP-5 is associated with depressive symptoms and cognition. The association of depressive symptoms with cognitive decline is conditional on IGFBP-5.